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Human Tumor Antigens Tn and Sialyl Tn Arise from Mutations in Cosmc

¹ Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia; and Departments of ² Obstetrics and Gynecology, ³ Biochemistry and Molecular Biology, ⁴ Pathology, and ⁵ Cell Biology, ⁶ Cancer Institute, University of Oklahoma Health Sciences Center, and ⁷ Oklahoma School of Sciences and Mathematics, Oklahoma City, Oklahoma

Requests for reprints: Richard D. Cummings or Tongzhong Ju, Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Room 4001, Atlanta, GA 30322. Phone: 404-727-6166; E-mail: rdcummi{at}emory.edu or tju{at}emory.edu.

Key Words: tumor markers • Tn, sialyl Tn • Cosmc • mutation • O-glycan • gastrointestinal cancers: colorectal • tumor markers and detection of metastasis

Neoplastic lesions typically express specific carbohydrate antigens on glycolipids, mucins, and other glycoproteins. Such antigens are often under epigenetic control and are subject to reversion and loss upon therapeutic selective pressure. We report here that two of the most common tumor-associated carbohydrate antigens, Tn and sialyl Tn (STn), result from somatic mutations in the gene Cosmc that encodes a molecular chaperone required for formation of the active T-synthase. Diverse neoplastic lesions, including colon cancer and melanoma-derived cells lines, expressed both Tn and STn antigen due to loss-of-function mutations in Cosmc. In addition, two human cervical cancer specimens that showed expression of the Tn/STn antigens were also found to have mutations in Cosmc and loss of heterozygosity for the cross-linked Cosmc locus. This is the first example of somatic mutations in multiple types of cancers that cause global alterations in cell surface carbohydrate antigen expression. [Cancer Res 2008;68(6):1636–46]

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				T. Ju, R. P. Aryal, C. J. Stowell, and R. D. Cummings Regulation of protein O-glycosylation by the endoplasmic reticulum-localized molecular chaperone Cosmc J. Cell Biol., August 12, 2008; 182(3): 531 - 542. [Abstract] [Full Text] [PDF]

				Correction: Cosmc Mutation in Cancer Cancer Res., April 15, 2008; 68(8): 3076 - 3076. [Full Text] [PDF]